1. Field of the Invention
The present invention relates to a process for the preparation of thiophene derivatives and novel thiophene derivatives, and in more detail, this invention relates to a process for preparing .alpha.-(2-thienyl)propionic acids which are useful as, for example, starting raw materials for the production of thioprofenic acid which is known as an anti-inflammatory agent, from 2-(dihaloacetyl)thiophenes which are easily obtainable by acetylation and halogenation of substituted or unsubstituted thiophenes. This invention also relates to novel compounds, i.e. 1-(2-thienyl)-1-dihalomethylethanols which are obtainable during the course of the preparation of .alpha.-(2-thienyl)propionic acids.
2. Description of the Prior Art
The processes for the preparation of .alpha.-(2-thienyl)propionic acids hitherto known in the art are (1) a process which comprises chloromethylation of thiophene by treating with aqueous formaldehyde in concentrated hydrochloric acid to obtain 2-thienylmethyl chloride, and introduction of cyano group treating with sodium cyanide to transfer into 2-thienylacetonitrile, then converting it to ethyl thienylcyanoacetate by ethoxycarbonation with diethyl carbonate in the presence of sodium metal, and then reacting the ester with methyl iodide in the presence of a base to prepare ethyl .alpha.-thienyl-.alpha.-cyanopropionate, then converting it to .alpha.-thienylpropionitrile by conducting hydrolysis and decarboxylation and then, further conducting hydrolysis of nitrile group to convert it to carboxyl group (M. Bercot-Vatteroni et al., Bull. Soc. Chim., France, 1820 (1961)) and (2) a process which comprises condensating ethyl chloroglyoxalate with thiophene by the liberation of hydrogen chloride, then conducting hydrolysis of the ester and reacting the product with a Grignard reagent thereby converting the carbonyl group to a methyl carbinol group and finally reducing the hydroxyl group to a hydrogen atom (F. Clemence et al., Eur. J. Med. Chem., (1974-9), 390). However, these processes are difficult to adopt as industrial processes for the production of .alpha.-(2-thienyl)propionic acids, since these processes need many reaction stages and are complicated and in process (1), obtainment of a starting material, i.e. thienylcyanoacetate is difficult.